1. Field of the Invention
The present invention relates to an ion-conducting adhesive composition that is suitable for skin contact during electrotransport of direct current stimulation and/or drug delivery. This adhesive composition minimizes the generation of electrolysis products such as hydrogen ions and/or hydroxyl ions, during use, thereby reducing pain and irritation of the skin. In the grounding position of a constant current drug delivery circuit, the adhesive composition will create a relative increase in the voltage gradient behind the drug. The adhesive composition is sufficiently weight bearing to hold small appliances and reserves for stimulation and/or drug delivery to the skin yet removes easily without leaving residue or causing irritation to the skin.
2. Description of the Art
Presently electrically conductive adhesive solid hydrogels and liquid gels are used in the medical field to provide an electrical interface to the skin of a subject to couple electrical signals into and/or out of the subject (e.g. for diagnostic and/or monitoring uses) and/or to couple electrical stimulus into the subject (e.g. for treatment and/or preventative uses.)
Perrault in U.S. Pat. No. 5,800,685 discloses hydrogels which include 40% or more, by weight, water and are particularly suitable for use in electronic medical devices such as sensing electrodes which are used for recording or monitoring, e.g. for ECG (electrocardiogram), EEG (electroencephalogram), and/or EMG (electromyogram), or as stimulation electrodes which are used to stimulate a subject, e.g. for transcutaneceous electrical nerve stimulation, for wound healing, for muscle stimulation (e.g. for physical therapy), for external pacing, for defibrillation or as electrosurgical and/or ablation grounding electrodes, or as electrotransport electrodes, e.g. for the iontophoresis or electrophoresis of drugs into a subject.
In particular, the technique of iontophoresis employs an electric field to mobilize ionic medicaments through the skin. This therapeutic modality allows for the introduction of substances into the tissues and blood stream of a patient without the necessity of hypodermic injection and its concomitant untoward effects, such as pain and risk of infection. Delivery of drugs via iontophoresis also presents the advantage of avoiding first-pass metabolism of a medicament. When a medicament is taken orally and absorbed from the digestive tract into the blood stream, the blood containing the medicament first percolates through the liver, a metabolically active organ, before entering the general circulation for delivery to the target tissue. Thus, much of the orally ingested medicament may be metabolically inactivated before it has a chance to exert its pharmacologic effect.
The usefulness of electrodes in medical procedures is limited, however, by a finite incidence of skin burns resulting from the passage of current through the skin. The primary causative factor of this skin burning is an electrochemical mechanism whereby the applied current causes electrolysis of water and generates either H+or OHxe2x88x92 ions, which cause pH changes that ultimately lead to a burning of the skin under the electrode. For example, in an iontophoresis procedure to mobilize a positively charged medicament through the skin, the medicament will be placed at the anode or positive electrode A negatively charged electrode or cathode will act as an indifferent or counter electrode. When current is applied to the iontophoresis system, the medicament will be driven toward and through the skin, but the application of the current at the positive electrode will also cause the following reaction:
2H2Oxe2x86x92O2+4H++4exe2x88x92
The H+ ions will move rapidly to the skin, decrease the pH of the aqueous environment to dangerous levels, and ultimately cause a burning of the skin. At the cathode, in this example, the indifferent or counter electrode, the following reaction occurs:
2H2O+2exe2x88x92xe2x86x92H2+2OHxe2x88x92
The OHxe2x88x92 ions move rapidly to the skin, increase the pH of the aqueous environment at the electrode to dangerous levels, and ultimately cause a burning of the skin under the negative electrode. In an iontophoresis procedure to mobilize a negatively charged medicament through the skin, the same reactions will occur at the anode and cathode, with the cathode impregnated with the medicament ions and the anode acting as the indifferent or counter electrode. In a typical application of current through electrodes in contact with the skin, the pH under the anode decreases to less than 1.5 (acidic), and the pH under the cathode increases to exceed 10 (basic). Application of current in an iontophoresis procedure, then, not only mobilizes the ionic medicament across the skin, but also causes the electrolysis of water and the generation of reactive H+ and OHxe2x88x92 ions that cause a burning of the skin. In addition, a substantial amount of current is wasted in driving the H+ and OHxe2x88x92 ions and the presence of these ionic species in the iontophoretic system aggravates the problem of quantification of the amount of medicament delivered during iontophoresis.
A substantial effort has been directed toward alleviating the problem associated with electrochemical burns in iontophoresis. One approach has been to introduce a buffer into the iontophoretic system. A buffer renders a solution more resistant to a change in pH following addition of acid (H+) or base (OHxe2x88x92) than does an equal volume of water. In this approach, a soluble buffer salt is included in the solution containing medicament ions.
This use of a buffer in an iontophoresis system, however, presents several problems. Firstly, buffer ion molecules and their complementary ions tend to be smaller and thus more mobile than the medicament ions. When current is applied to an iontophoretic system containing a buffer, the buffer ions will move more rapidly toward and through the skin than the medicament ions, and it is more difficult to quantify the amount of medicament driven through the skin. Although a buffer incorporated into an iontophoresis system could successfully scavenge undesirable H+ and OHxe2x88x92 ions and reduce burning of the skin, the problems associated with mobile buffer ions overcome any advantage this approach might have.
Various iontophoresis devices are known, some of which include approaches that attempt to solve the problems associated with the generation of irritating hydrogen and hydroxyl ions and/or the use of buffer systems based small molecules such as the common salts of weak acids and/or weak bases.
For example, U.S. Pat. No. 5,668,356 to Jevne et al discloses amphoteric copolymers having alternating acid and basic monomer units for use in iontophoresis devices.
Cormier et al in U.S. Pat. No. 5,624,415, discloses a method for minimizing skin irritation and/or erythema in an iontophoresis device by maintaining the anode reservoir at a pH about 4 and/or the cathode reservoir at a pH below 4 and/or monitoring the potassium efflux level in said reservoirs.
Gyory et al in U.S. Pat. Nos. 5,234,991; 5,240,995 and 5,344,394 disclose a two phase adhesive for use in an iontophoresis device comprising a hydrophilic polymer phase. In addition, Gyory et al in U.S. Pat. No. 5,668,170 disclose the use of xe2x80x9cpermeation enhancersxe2x80x9d including quaternary ammonium salts to enhance electrotransport in an electrotransport delivery device.
Atanasoka et al disclose an iontophoresis device comprising a buffer component including a pH buffering agent heterogeneously dispersed in an absorbent material. The pH buffering agent may be an ion exchange material. See U.S. Pat. Nos. 5,857,993; 5,871,461 and 5,941,843. (See also, U.S. Pat. No. 4,973,303 to Johnson et al and U.S. Pat. No. 5,766,144 to Lai et al which also disclose the use of ion exchange resins as a pH buffer for an electrode useful in iontophoresis.) Atanansoka et al also disclose a pH buffered electrode which may be used in an iontophoresis device comprising a pH buffer chemically bonded to a foam. Said pH buffer may comprise a means for scavenging hydrogen ions without releasing ions, i.e. a xe2x80x9cproton spongexe2x80x9d. See U.S. Pat. Nos. 5,788,666 and 5,840,056; respectively.
Thus, it is clear that efforts continue to overcome the problems of skin irritation resulting from the use of iontophoresis devices, as well as other electrotransport devices which are utilized to transport medicaments through the skin of a subject.
The present invention provides an electrically conductive adhesive hydro gel comprising from about 15 to about 60%, by weight of a cationic polymer prepared by the polymerization of a monomer having the formula: 
wherein m is an integer of from 1 to 3; R1, R2 and R3 are selected from the group consisting of H and hydrocarbyl radicals having from 1 to 15 carbon atoms and Xxe2x88x92 is an anion and from about 5 to less than about 40% water, by weight.
The above polymer is of the formula 
wherein m is an integer of from 1 to 3; R1, R2 and R3 are selected from the group consisting of hydrogen and selected from the group consisting of H and hydrocarbyl radicals having from 1 to 15 carbon atoms, and n is a number greater than 1000.
In particular, the present invention provides an electrically powered iontophoretic medicament delivery device including a donor electrode assembly, a counter electrode assembly and a source of electrical power adapted to be electrically connected to the donor electrode assembly and the counter electrode assembly, the donor electrode assembly including the medicament reservoir containing the above hydrogel and the medicament reservoir being adapted to be placed in medicament transmitting relation with a body surface by adhering said medicament reservoir to said body surface by means of said hydrogel; and
a donor electrode adapted to be electrically connected to the source of electrical power, the donor electrode being in electrical contact with the medicament reservoir.